Is urinary myelin basic protein the key to understanding the role of vitamin D supplementation in paediatric overactive bladder-dry? Results from a three-stage clinical investigation.

To validate urinary myelin basic protein (uMBP) as a mechanism-based diagnostic and prognostic biomarker for paediatric overactive bladder-dry (OAB-dry) in children with 25-hydroxyvitamin D (25[OH]D) levels of <35 ng/mL, and to explore whether vitamin D supplementation (VDS) targets a reversible neuromyelination pathway. This three-phase study comprised: (i) discovery of candidate biomarkers via urinary proteomics; (ii) diagnostic validation in a cross-sectional cohort (n = 216); and (iii) a 12-week multicentre randomised controlled trial (RCT, n = 180). Children with OAB-dry and 25(OH)D level of <35 ng/mL were randomised (1:1) to receive high-dose VDS (2400 IU/day) plus standard urotherapy (SU) or solifenacin (5 mg/day) plus SU. The primary outcome was the change in daily voiding frequency. We evaluated the interaction between baseline uMBP/creatinine ratio (uMBP/Cr) and treatment response and performed moderated mediation analysis to assess the mechanistic role of uMBP/Cr reduction. The uMBP/Cr was significantly elevated in paediatric OAB-dry with vitamin D levels of <35 ng/mL and showed a strong negative correlation with 25(OH)D levels (ρ = -0.69, P < 0.001). It achieved an area under the curve of 0.80 for diagnosing paediatric OAB with 25(OH)D levels of <35 ng/mL. In the RCT, VDS + SU demonstrated superior efficacy compared to solifenacin + SU in reducing voiding frequency (adjusted difference: 2.7 voids/day, P < 0.001). Importantly, baseline uMBP/Cr significantly modified the treatment effect: higher baseline levels predicted a greater reduction in symptoms with VDS + SU (Ptrend < 0.001). Furthermore, the reduction in uMBP/Cr during treatment mediated 35.2% of the therapeutic benefit of VDS on voiding frequency, supporting a treatment mechanism involving myelin restoration. Urinary MBP serves as a predictive biomarker for a distinct 'neuro-vulnerable' paediatric OAB-dry subtype, characterised by 25(OH)D levels of <35 ng/mL. These findings position uMBP as a potential tool for precision treatment stratification and suggest that paediatric OAB may represent a sentinel sign of underlying neural axis vulnerability associated with low vitamin D status.